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Population pharmacokinetic modeling of dolutegravir/lamivudine to support a once-daily fixed-dose combination regimen in virologically suppressed adults living with HIV-1
This study is registered with ClinicalTrials.gov as NCT03446573.PMID:38587380 | DOI:10.1128/aac.01504-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 8, 2024 Category: Microbiology Authors: Hardik Chandasana Rajendra Singh Kimberly Adkison Mounir Ait-Khaled Teodora Pene Dumitrescu Source Type: research

Extended blood stage sensitivity profiles of Plasmodium cynomolgi to doxycycline and tafenoquine, as a model for Plasmodium vivax 
Antimicrob Agents Chemother. 2024 Apr 8:e0028024. doi: 10.1128/aac.00280-24. Online ahead of print.ABSTRACTTesting Plasmodium vivax antimicrobial sensitivity is limited to ex vivo schizont maturation assays, which preclude determining the IC50s of delayed action antimalarials such as doxycycline. Using Plasmodium cynomolgi as a model for P. vivax, we determined the physiologically significant delayed death effect induced by doxycycline [IC50(96 h), 1,401 ± 607 nM]. As expected, IC50(96 h) to chloroquine (20.4 nM), piperaquine (12.6 µM), and tafenoquine (1,424 nM) were not affected by extended exposure.PMID:38587391 | DOI...
Source: Antimicrobial Agents and Chemotherapy - April 8, 2024 Category: Microbiology Authors: Peter Christensen Rosy Cinzah Rossarin Suwanarusk Adeline Chiew Yen Chua Osamu Kaneko Dennis E Kyle Htin Lin Aung Jessica Matheson Pablo Bifani Laurent R énia Gregory M Cook Georges Snounou Bruce Russell Source Type: research

Influenza C virus susceptibility to antivirals with different mechanisms of action
Antimicrob Agents Chemother. 2024 Apr 8:e0172723. doi: 10.1128/aac.01727-23. Online ahead of print.ABSTRACTAntiviral susceptibility of influenza viruses was assessed using a high-content imaging-based neutralization test. Cap-dependent endonuclease inhibitors, baloxavir and AV5116, were superior to AV5115 against type A viruses, and AV5116 was most effective against PA mutants tested. However, these three inhibitors displayed comparable activity (EC50 8-22 nM) against type C viruses from six lineages. Banana lectin and a monoclonal antibody, YA3, targeting the hemagglutinin-esterase protein effectively neutralized some, bu...
Source: Antimicrobial Agents and Chemotherapy - April 8, 2024 Category: Microbiology Authors: Anton Chesnokov Andrei A Ivashchenko Yoko Matsuzaki Emi Takashita Vasiliy P Mishin Alexandre V Ivachtchenko Larisa V Gubareva Source Type: research

Transcriptomic responses to antibiotic exposure in Mycobacterium tuberculosis 
Antimicrob Agents Chemother. 2024 Apr 8:e0118523. doi: 10.1128/aac.01185-23. Online ahead of print.ABSTRACTTranscriptional responses in bacteria following antibiotic exposure offer insights into antibiotic mechanism of action, bacterial responses, and characterization of antimicrobial resistance. We aimed to define the transcriptional antibiotic response (TAR) in Mycobacterium tuberculosis (Mtb) isolates for clinically relevant drugs by pooling and analyzing Mtb microarray and RNA-seq data sets. We generated 99 antibiotic transcription profiles across 17 antibiotics, with 76% of profiles generated using 3-24 hours of antib...
Source: Antimicrobial Agents and Chemotherapy - April 8, 2024 Category: Microbiology Authors: Husain Poonawala Yu Zhang Sravya Kuchibhotla Anna G Green Daniela Maria Cirillo Federico Di Marco Andrea Spitlaeri Paolo Miotto Maha R Farhat Source Type: research

Prospective validation of a model-informed precision dosing tool for vancomycin treatment in neonates
Antimicrob Agents Chemother. 2024 Apr 5:e0159123. doi: 10.1128/aac.01591-23. Online ahead of print.ABSTRACTWe recruited 48 neonates (50 vancomycin treatment episodes) in a prospective study to validate a model-informed precision dosing (MIPD) software. The initial vancomycin dose was based on a population pharmacokinetic model and adjusted every 36-48 h. Compared with a historical control group of 53 neonates (65 episodes), the achievement of a target trough concentration of 10-15 mg/L improved from 37% in the study to 62% in the MIPD group (P = 0.01), with no difference in side effects.PMID:38578080 | DOI:10.1128/aac.0159...
Source: Antimicrobial Agents and Chemotherapy - April 5, 2024 Category: Microbiology Authors: Riste Kalamees Hiie Soeorg Mari-Liis Ilmoja Kadri Margus Irja Lutsar Tuuli Metsvaht Source Type: research

ABC transporter inhibition by beauvericin partially overcomes drug resistance in Leishmania tropica 
In this study, the ability of beauvericin (BEA) to overcome ABC transporter-mediated resistance of Leishmania tropica to ML was assessed. In addition, the transcription profile of genes involved in resistance acquisition to ML was inspected. Finally, we explored the efflux mechanism of the drug and inhibitor. The efficacy of ML against all developmental stages of L. tropica in the presence or absence of BEA was evaluated using an absolute quantification assay. The expression of resistance genes was evaluated, comparing susceptible and resistant strains. Finally, the mechanisms governing the interaction between the ABC tran...
Source: Antimicrobial Agents and Chemotherapy - April 4, 2024 Category: Microbiology Authors: Charbel Al Khoury Sergio Thoumi Sima Tokajian Aia Sinno Georges Nemer Mark El Beyrouthy Kelven Rahy Source Type: research

Efflux pump effects on levofloxacin resistance in Mycobacterium abscessus 
Antimicrob Agents Chemother. 2024 Apr 4:e0134823. doi: 10.1128/aac.01348-23. Online ahead of print.ABSTRACTMycobacterium abscessus (M. abscessus) inherently displays resistance to most antibiotics, with the underlying drug resistance mechanisms remaining largely unexplored. Efflux pump is believed to play an important role in mediating drug resistance. The current study examined the potential of efflux pump inhibitors to reverse levofloxacin (LFX) resistance in M. abscessus. The reference strain of M. abscessus (ATCC19977) and 60 clinical isolates, including 41 M. abscessus subsp. abscessus and 19 M. abscessus subsp. massi...
Source: Antimicrobial Agents and Chemotherapy - April 4, 2024 Category: Microbiology Authors: Tianlu Teng Suting Chen Fengmin Huo Junnan Jia Liping Zhao Guanglu Jiang Fen Wang Naihui Chu Hairong Huang Source Type: research

The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum 
Antimicrob Agents Chemother. 2024 Apr 3:e0160923. doi: 10.1128/aac.01609-23. Online ahead of print.ABSTRACTThe increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. ...
Source: Antimicrobial Agents and Chemotherapy - April 3, 2024 Category: Microbiology Authors: Masaki Ishii Tsuyoshi Yamada Kazuki Ishikawa Koji Ichinose Michel Monod Shinya Ohata Source Type: research

Characterization of Acinetobacter baumannii-calcoaceticus complex isolates and microbiological outcome for patients treated with sulbactam-durlobactam in a phase 3 trial (ATTACK)
This report describes the characterization of the baseline ABC isolates from patients enrolled in ATTACK, including an analysis of the correlation of microbiological outcomes with SUL-DUR MIC values and the molecular drivers of SUL-DUR resistance.PMID:38567976 | DOI:10.1128/aac.01698-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 3, 2024 Category: Microbiology Authors: Alita A Miller Samir H Moussa Sarah M McLeod Source Type: research

A randomized assessors-blind clinical trial to evaluate the safety and the efficacy of albendazole alone and in combination with mebendazole or pyrantel for the treatment of Trichuris trichiura infection in school-aged children in Lambar éné and surroundings
Antimicrob Agents Chemother. 2024 Apr 2:e0121123. doi: 10.1128/aac.01211-23. Online ahead of print.ABSTRACTHelminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat Trichuris trichiura infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with T. trichiura. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and ...
Source: Antimicrobial Agents and Chemotherapy - April 2, 2024 Category: Microbiology Authors: Paul Alvyn Nguema Moure Moustapha Nzamba Maloum G édéon Prince Manouana Rom éo-Aimé Laclong Lontchi Mirabeau Mbong Ngwese Jean Ronald Edoa Jeannot Fr éjus Zinsou Brice Meulah Saidou Mahmoudou Elsy Mirna N'noh Dansou Yabo Josiane Honkpehedji Bayode Ro Source Type: research

Nationwide genome surveillance of carbapenem-resistant Pseudomonas aeruginosa in Japan
This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.PMID:38564665 | DOI:10.1128/aac.01669-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 2, 2024 Category: Microbiology Authors: Hirokazu Yano Wataru Hayashi Sayoko Kawakami Sadao Aoki Eiko Anzai Hui Zuo Norikazu Kitamura Aki Hirabayashi Toshiki Kajihara Shizuo Kayama Yo Sugawara Koji Yahara Motoyuki Sugai Source Type: research